Desaturation is a necessary step in the modification of essential fatty acids linoleic and linolenic acids to arachidonic and docosahexaenoic acid, respectively. The levels of these fatty acids are lowered by ethanol consumption in blood cells, liver and brain. The mechanisms underlying the disruption of essential fatty acid levels in these tissues is largely unknown. One possible explanation for this alcohol-induced deficiency is inhibition of elongation/desaturation of 18-carbon essential fatty acids by alcohol. A stable isotope gas chromatography/mass spectrometry (GC/MS) method has been developed that allows for the in vivo examination of these processes. This technique has improved the sensitivity of the method by several orders of magnitude and has made possible non-invasive metabolic studies in large animals. Studies in rats, cats and rhesus monkeys have indicated that all mammals have elongation and desaturation capability and that it may be monitored in the blood supply. This approach has made possible human trials in which we will investigate the effects of alcohol abuse and withdrawal as well as diet on desaturation and chain elongation.